Neural substrates underlying vestibular compensation: contribution of peripheral versus central processing

Abstract

The vestibulo-ocular reflex (VOR), which functions to stabilize gaze and ensure clear vision during everyday activities, shows impressive adaptation in response to environmental requirements. In particular, the VOR exhibits remarkable recovery following the loss of unilateral labyrinthine input as a result of injury or disease. The relative simplicity of the pathways that mediate the VOR, make it an excellent model system for understanding the changes (learning) that occur in the brain following peripheral vestibular loss to yield adaptive changes. This mini review considers the findings of behavioral, single unit recording and lesion studies of VOR compensation. Recent experiments have provided evidence that the brain makes use of multiple plasticity mechanisms (i.e., changes in peripheral as well as central processing) during the course of vestibular compensation to accomplish the sensory-motor transformations required to accurately guide behavior.

Figure 1

Compensation in the VOR response following unilateral labyrinthectomy in macaque monkeys. A. Response to sinusoidal rotations at 0.5 (red), 10 (blue), and 15 (green) Hz (peak velocity of 40 °/s) before (left) and 39 days (right) after lesion. Traces are offset from their zero eye velocity (cross) for clearer presentation. Light colors show data points and the dark line is fitted to the points using the 3^rd order equation. Dashed lines have a slope of -1 (i.e., perfect VOR response). Note that even at this late stage after labyrinthectomy, responses gains become increasingly attenuated with rising frequency for ipsilesional half-cycles. B. Mean VOR gain elicited by transient head perturbations before and at different days after lesion. Head perturbations reached peak accelerations of 3,000, 8,000, and 12,000 °/s². Responses reach steady-state levels by around day 18. Error bars represent standard error of the mean.

Figure 2

Response of vestibular-nerve afferents innervating the semicircular canals before and after unilateral labyrinthectomy in macaque monkeys. A. Response of afferents as a function of frequency. Sensitivity and phase lead(relative to velocity) of responses during sinusoidal rotations with frequencies of 0.5 to 15 Hz (±50°/s) before (continuous lines, filled symbols) and after (dashed lines, empty symbols) labyrinthectomy. B. Average response of irregular and regular afferents during rotations with velocities of up to 500 °/s, before (blue lines) and after lesion (red lines). Light colored areas represent the SE of the responses. Differences in each group were not significant under the two conditions. C. Comparison of the distribution of afferents based on the regularity of the resting discharge (measured by the normalized coefficient of variation, CV*) before (filled red bars) and after (empty blue bars) lesion. There was a slight increase in the percentage of irregular afferents following lesion.

Figure 3

Compensation in the VOR response following unilateral labyrinthectomy in mice during sinusoidal rotations. A. Normalized VOR gain (re. prelesion value) in control mice. For both contra- and ipsilesional rotations, VOR responses showed compensation, reaching normal values in about 10 days. B. Normalized VOR gain (re. prelesion value) in cerebellar deficient mice. While contralesional VOR responses reached normal values in ∼10 days, ipsilesional responses did not show an improvement after the first week and remained lower than normal. Asterisks on B show significant differences between control and cerebellar deficient mice (p< 0.05).

Figure 4

Direct and indirect VOR pathways. Vestibular nuclei receive direct inputs from the vestibular-nerve afferents, as well as indirect inputs from the cerebellum and contralateral vestibular nuclei. Signals cross the midline to the abducens neurons on the other side, which are then transmitted to the eye muscles. A feedback loop carries signals through the vestibular efferents from the vestibular nuclei to the periphery.